Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated three aldolase isozymes (aldolase A, B, and C) in human lung cancer by using an indirect peroxidase labeled antibody method. We used 27 tissue samples obtained at surgical operations which were fixed in periodate-lysine-4% paraformaldehyde (PLP) solution, and embedded in optimum cutting temperature (OCT) compound. They were 11 adenocarcinomas, 9 squamous cell carcinomas, 3 large cell carcinomas, 3 small cell carcinomas, and 1 adenosquamous carcinoma. Aldolase A and C expressed intensely positive stainings in the cytoplasm of cancer cells compared with normal lung tissues, and its positivities were 81% respectively. However, Aldolase B showed almost negative staining, and its positivities were only 41%. These rates had no relation to the histological types or pathological stages of lung cancers, and suggested that human lung cancer contained increased levels of aldolase A, and C.
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PMID:[An immunohistochemical study on three aldolase isozymes in human lung cancer]. 131 19

Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.
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PMID:Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting. 166 19

The aldolase isozymes A, B, and C in tumor tissues (63) and sera (104) of patients with lung cancer were determined with an enzyme immunoassay system, compared with normal lung tissues (13), and the sera of normal healthy subjects (100). Tissue aldolase A and C concentrations were enhanced in 83% (52/63) and 51% (32/63) of patients with lung cancer, respectively, regardless of histologic type or stage (P less than 0.01). But aldolase B was not elevated in tissue levels. In the sera of patients with lung cancer, there were no significant elevations of the isozymes. Immunohistochemically aldolase A and C stained more intensely in the cytoplasm of lung cancer cells than those in normal tissues. These results indicate lung cancer cells contain enhanced tissue levels of aldolase A and C.
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PMID:Immunochemical and immunohistochemical studies on three aldolase isozymes in human lung cancer. 200 36

Enzyme patterns characteristic of fetal tissue have been noted in some experimental tumor models, particularly in hepatomas. In this study we undertook to determine whether biochemical evidence of a similar reversion could be detected in tumors of other human organs. As marker, we chose to use the aldolase isoenzymes A, B and C, for which distinct adult and fetal tissue patterns have been described. Using monospecific antibodies, we determined the aldolase isoenzyme pattern in a variety of human organs ranging in age from 14 to 40 weeks of gestation, in the 2- to 3-month postnatal period and in adults. In addition, 19 breast cancers, 19 primary lung cancers and 8 kidney cancers were examined. Our studies on breast cancer revealed three apparently distinct groups -- one showing primarily the A isoenzyme type (6 cases), a second containing mainly A with considerable quantities of B and C isoenzymes (9 cases) and a third group (4 cases) which may contain a different isoenzyme altogether since the combined activity of the three known forms was less than 100% in each case. In lung cancer, fetal characteristics could be substantiated since in fetal and adult lung tissue, the isoenzyme pattern is almost identical; 3 out of 19 cases showed substantial quantities of the B isoenzyme. In kidney tumors, a reversion to the A form with an appreciable fraction of the C form was found, which is similar to the fetal pattern.
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PMID:Aldolase isoenzyme patterns during human ontogeny and in lung, kidney and breast cancer. 741 92

In the present study, we have assessed the chemopreventive effect of capsaicin (CAP) on glucose metabolism with reference to blood glucose and liver glycogen levels, key glycolytic, and gluconeogenic enzymes along with electron transport chain (ETC) complexes during benzo(a)pyrene (B(a)P)-induced lung cancer in Swiss albino mice. B(a)P (50 mg kg(-1) body weight)-induced lung cancer animals showed marked decline in blood glucose levels, glycogen levels, elevations in the activities of key glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase), and gluconeogenic enzymes (glucose-6-phosphatase and fructose-6-phosphatase) together with a decrease in the activities of ETC complexes. Supplementation of CAP (10 mg kg(-1) body weight) inhibited all the above alterations during lung cancer and restored near normalcy. Histochemical analysis by periodic acid Schiff's staining further confirmed the biochemical findings that highlighted the chemopreventive action of CAP during B(a)P-induced experimental lung tumourigenesis.
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PMID:Effect of capsaicin on glucose metabolism studied in experimental lung carcinogenesis. 1941 59

Dermatomyositis represents an idiopathic inflammatory connective-tissue disease, characterized by inflammation of the muscles and the skin. There is a high incidence of malignancy in patients with dermatomyositis. The main purpose of the present paper is to describe and underline the clinical significance of dermatomyositis manifestations as a precursor and early clinical signs of small cell lung cancer. A physical examination, laboratory tests, anti-Jo-1 antibody and muscle biopsy were performed. The most important findings were SGOT 284 IU/L, CPK 11083 IU/L, aldolase 76.3 IU/L (normal values <7.6). The patient was treated with chemotherapy and a significant improvement of clinical and laboratory findings were noted. The diagnosis of lung cancer could be correlated with the clinical existence of dermatomyositis. Increased awareness is needed regarding the association of dermatomyositis with malignancies in order to achieve correct and timely diagnosis of the underling cancer.
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PMID:Dermatomyositis as an early manifestation and a significant clinical precursor of lung cancer: report of a rare case and review of the current literature. 2338 13

Muscle fructose 1,6-bisphosphate aldolase (ALDA) is a glycolytic enzyme which may localize both in nuclei and cytoplasm of cells, however its role in the nuclei is unclear. Here, we demonstrate the links between subcellular localization of ALDA and the cell cycle progression as well as the availability of energetic substrates. Results of our studies indicate that nuclear localization of ALDA correlates with the proliferative activity of the cells and with the expression of Ki-67, a marker of proliferation, both in the KLN-205 (mouse lung cancer cells) and human squamous cell lung cancer cells (hSCC). Chemically-induced block of cell cycle entry in S phase and the inhibition of transcription stimulate removal of ALDA from cells nuclei suggesting that nuclear ALDA is involved in cells proliferation. On the other hand, subcellular distribution of the enzyme also depends on the stress and pro-survival signals mediated by the Akt and the p38 pathways and, in non-proliferating cells, on the availability of glucose and lactate. The results presented here point to ALDA as a factor involved in the regulation of cells proliferation.
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PMID:Nuclear localization of aldolase A correlates with cell proliferation. 2388 27

Uncoupling protein 1 (UCP1) is a proton transporter/channel residing on the inner mitochondrial membrane and is involved in cellular heat production. Using immunohistochemistry, we investigated the expression of UCP1 and UCP3 in a series of 98 patients with non-small cell lung cancer (NSCLC) treated with surgery. Expression patterns were correlated with histopathological variables, prognosis, and the expression of enzymes/proteins related to cell metabolism. Bronchial epithelium did not express UCP1 or UCP3, while alveolar cells strongly expressed UCP1. In tumors, strong expression of UCP1 and UCP3 was recorded in 43/98 (43.8%) and 27/98 (27.6%) cases, respectively. UCP1 was significantly associated with squamous cell histology (P = 0.05), whilst UCP3 was more frequently overexpressed in large cell carcinomas (P = 0.08), and was inversely related to necrosis (P = 0.009). In linear regression analysis, UCP1 was directly related to markers of glycolysis [hexokinase (HXKII) and phosphofructokinase (PFK1)] and anaerobic glucose metabolism [pyruvate dehydrogenase kinase (PDK1) and lactate dehydrogenase (LDH5)]. UCP3 was directly linked with a glucose transporter (GLUT2), monocarboxylate transporter (MCT2), glycolysis markers (PFK1 and aldolase), and with the phosphorylation of pyruvate dehydrogenase (pPDH). Kaplan-Meier survival analysis showed that UCP3 was significantly related to poor prognosis in squamous cell carcinomas (P = 0.04). UCP1 and UCP3 are overexpressed in a large subgroup of non-small cell lung tumors and their expression coincides with increased glucose absorption, intensified glycolysis, and anaerobic glucose usage. Whether UCPs are targets for therapeutic interventions in lung cancer is a hypothesis that demands further investigation.
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PMID:Thermogenic protein UCP1 and UCP3 expression in non-small cell lung cancer: relation with glycolysis and anaerobic metabolism. 2937 6

A 74-year-old man was administered nivolumab to treat recurrent squamous cell carcinoma of the lungs. He developed fatigue, redness on the front of his neck, muscle weakness, and difficulty in swallowing after receiving the third course of nivolumab. Physical and neurological examinations showed proximal limb muscle weakness, periorbital erythema, and erythema of the front of his neck as well as fingers. Laboratory investigations revealed elevated serum CK and aldolase levels, and he was diagnosed with dermatomyositis. We initiated steroid pulse therapy and intravenous immunoglobulin therapy; however, he died of advanced lung cancer. Immune checkpoint inhibitor-induced neuromuscular disease is increasingly being observed in clinical practice. We report a rare case of dermatomyositis with squamous cell carcinoma of the lungs secondary to nivolumab treatment.
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PMID:[Dermatomyositis with squamous cell carcinoma of the lungs secondary to nivolumab treatment: a case report]. 3311 92